Genocea Unveils Protective Therapeutic Vaccine for Herpes Simplex Virus Type 2 (HSV-2)

  • Candidate vaccine reduced duration and severity of symptoms in preclinical models
  • Data validate T cell vaccine strategy for Herpes Simplex Virus type 2 (HSV-2)
  • Data will be presented this week at 37th Annual International Herpesvirus Workshop

CAMBRIDGE, Mass.--()--Genocea Biosciences announced today the presentation of new data supporting its novel approach to developing a first-in-class, protein subunit therapeutic vaccine for Herpes Simplex Virus type 2 (HSV-2). The data, to be presented this week at the 37th annual International Herpesvirus Workshop (IHW) in Calgary, Alberta, highlight antigens identified through Genocea’s unique technology platform that stimulate T cell immune responses to HSV-2. A candidate vaccine consisting of these antigens reduced viral shedding and clinical disease when tested in a preclinical model of HSV-2 infection.

“We are highly encouraged by these data, which mark the first time a protein subunit therapeutic vaccine has been shown to affect disease and viral shedding significantly in this model,” said Jessica Flechtner, Ph.D., Vice President, Research, Genocea Biosciences. “As we advance toward the clinic, these data give us great confidence in our lead vaccine candidate, and suggest that we have identified full protein antigens that stimulate a balanced and effective B and T cell immune response.”

In one of two studies presented, Genocea researchers studied the T cell immune responses to each HSV-2 protein among patients with HSV-2 infection or exposure. Using ATLAS™, Genocea’s proprietary high-throughput screening platform, they identified HSV-2 proteins (or antigens) associated with protective immune responses in volunteers who had no evidence of infection but had been exposed to HSV-2, or who had relatively mild HSV-2 infections. Patients with severe disease, as indicated by multiple outbreaks of genital herpes, had weaker or no responses to these same proteins.

Genocea advanced one antigen, ICP4, and evaluated its therapeutic effectiveness when formulated as a vaccine with glycoprotein D in subsequent studies. In a therapeutic efficacy model, vaccinated guinea pigs showed a 45 percent reduction in duration, and a 55 percent reduction in severity, of clinical symptoms. Furthermore, no measurable virus was found in the reproductive tract of the vaccinated animals after completion of the immunization course.

About the Studies

Identification of novel virus-specific T cell antigens in HSV-2 seropositive and seronegative persons using a high-throughput proteomic screening platform

A high-throughput proteomic screening technology that identifies proteins to which the immune system generates T cell responses after natural exposure was used to compare T cell immune responses among patients exposed to or infected with HSV-2 and who exhibit a range of disease severities. HSV-2 infected subjects were recruited and categorized according to the following phenotypes: HSV-2 infected with (1) ≥ 4, (2) < 3, (3) no clinical recurrences/year and (4) HSV-2 exposed but seronegative. Peripheral CD4+ and CD8+ T cells and antigen presenting cells were enriched and used to screen a library expressing the entire HSV-2 proteome. Antigen-specific responses were measured by IFNγ secretion by ELISA. Antigens were compared across clinical phenotypes by both magnitude and frequency of responses to each expressed protein. Proteins that elicited CD4+ and/or CD8+ T cell responses of greater frequency and magnitude among cohorts (3) and (4) compared to cohorts (1) and (2) were: gL, UL36, UL40, ICP27, ICP34.5, ICP4, and ICP0.

An adjuvanted HSV-2 subunit vaccine formulation elicits a potent T cell response in mice and is an effective therapeutic vaccine in the guinea pig model of genital herpes

A successful therapeutic vaccine depends on both the selection of antigen and the method of presentation to the immune system. A virus-specific T cell antigen (ICP4) was identified that was more frequently associated with persons exposed to HSV-2 who remained seronegative and HSV-2 seropositive subjects who demonstrated no lesion outbreaks, compared with HSV-2 seropositive subjects with recurrences. In the present study, we characterized the immune response in mice to a candidate vaccine, ICP4383-766 and gD2 (ΔTMR341-363), formulated with Matrix-M™, an adjuvant that promotes T cell responses. Two immunizations with this vaccine three weeks apart elicited CD4+ and CD8+ T cell responses that persisted for 90 days. IgG antibody responses were also induced, with a log10 titer of 4.4 (gD2) and 4.5 (ICP4). gD2-specific antibody was neutralizing, with a log10 titer of 2.8. Therapeutic efficacy was then examined in a guinea pig genital herpes model. Animals were infected intravaginally, immunized three times and examined for genital disease symptoms. Vaccinated animals showed a 45% reduction in lesion days (p <0.01) with severity scores reduced by 55% (p <0.001) compared to the adjuvant control. Furthermore, no virus was detected by real-time PCR in genital swabs after three vaccine immunizations (p < 0.05). Our results indicate that antigens selected by examination of clinical phenotypes demonstrated immunogenicity and efficacy in animal models, making this a desirable vaccine formulation for clinical trial testing.

About HSV-2

Herpes simplex virus type 2 (HSV-2), the most common cause of genital herpes, is a sexually transmitted disease that is estimated to infect more than 500 million people worldwide, and one out of six people aged 15 to 49. In the U.S. alone, an estimated 50-60 million people are affected. HSV-2 infection can cause recurring, painful genital sores, and can be stigmatizing and produce considerable psychological distress in patients. The disease is particularly severe in immunosuppressed patients and poses significant risk to newborns if it is transmitted from mothers during birth. While antiviral drugs are used widely to treat HSV-2, there is neither a cure nor a vaccine for this disease.

About Genocea Biosciences

Genocea Biosciences is harnessing the power of the T cell immunity to develop the next generation of vaccines. T cells are increasingly recognized as a critical element of a protective immune response to a wide range of infectious disease pathogens, but are difficult to target using traditional vaccine discovery methods. Genocea is uniquely able to identify and employ T cell antigens using ATLAS™, its proprietary technology platform, which mimics human T cell immune response in the laboratory, potentially improving the effectiveness of vaccine candidates and drastically reducing the time needed to create them.

For more information, please visit the company’s website at Genocea.com.

Contacts

Feinstein Kean Healthcare
Jessica Rowlands, 202-729-4089
jessica.rowlands@fkhealth.com

Contacts

Feinstein Kean Healthcare
Jessica Rowlands, 202-729-4089
jessica.rowlands@fkhealth.com